TY  - JOUR
A1  - Michels, Birgitta E.
A1  - Mosa, Mohammed Hossameldin
A1  - Grebbin, Britta Moyo
A1  - Yepes, Diego
A1  - Darvishi, Tahmineh
A1  - Hausmann, Johannes
A1  - Urlaub, Henning
A1  - Zeuzem, Stefan
A1  - Kvasnicka, Hans Michael
A1  - Oellerich, Thomas
A1  - Farin, Henner
T1  - Human colon organoids reveal distinct physiologic and oncogenic Wnt responses
T2  - Journal of experimental medicine
N2  - Constitutive Wnt activation upon loss of Adenoma polyposis coli (APC) acts as main driver of colorectal cancer (CRC). Targeting Wnt signaling has proven difficult because the pathway is crucial for homeostasis and stem cell renewal. To distinguish oncogenic from physiological Wnt activity, we have performed transcriptome and proteome profiling in isogenic human colon organoids. Culture in the presence or absence of exogenous ligand allowed us to discriminate receptor-mediated signaling from the effects of CRISPR/Cas9-induced APC loss. We could catalog two nonoverlapping molecular signatures that were stable at distinct levels of stimulation. Newly identified markers for normal stem/progenitor cells and adenomas were validated by immunohistochemistry and flow cytometry. We found that oncogenic Wnt signals are associated with good prognosis in tumors of the consensus molecular subtype 2 (CMS2). In contrast, receptor-mediated signaling was linked to CMS4 tumors and poor prognosis. Together, our data represent a valuable resource for biomarkers that allow more precise stratification of Wnt responses in CRC.
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/54486
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-544866
SN  - 1540-9538
SN  - 1540-9358
N1  - © 2019 Michels et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
VL  - 216
IS  - 3
SP  - 704
EP  - 720
PB  - Rockefeller Univ. Press
CY  - New York, NY
ER  -